1. Field of the Invention
The present invention relates to the use of arbutin monoesters as depigmenting or bleaching agents in a composition for topical application, in particular a cosmetic and/or dermatological composition, as well as to the use of these arbutin esters in and/or for the manufacture of a cosmetic and/or dermatological composition, as a tyrosinase inhibitor and/or as a melanin-synthesis inhibitor. More particularly, the present invention relates to a process for depigmenting and/or bleaching the skin, hairs and head hair, using such arbutin monoesters.
2. Description of the Background
The color of the skin depends on different factors and, in particular, the seasons of the year, race and sex, and it is mainly determined by the concentration of melanin produced by the melanocytes. In addition, at different periods in their lives, certain individuals develop darker and/or more colored blemishes on the skin, especially on the hands, making the skin non-uniform in appearance. These blemishes are also caused by a large concentration of melanin in the keratinocytes at the skin surface.
In the same way, the color of hair and head hair is attributable to the presence of melanin. When hair or head hair is dark, certain people wish to have them lighter. This is particularly advantageous for hairs which are less visible when they are light than when they are dark.
For several years, a desired objective has been to decrease and/or slow down the production of melanin in order to depigment or bleach the skin, by acting on one or more of the points in the intracellular biochemical synthesis of melanin.
The mechanism for the formation of skin pigmentation, and pigmentation of hair and head hair, that is to say, the formation of melanin, is particularly complex and schematically involves the following main steps:
Tyrosine.fwdarw.Dop.fwdarw.Dopaquinone.fwdarw.Dopachrome.fwdarw.Melanin PA1 in which R is a linear or branched, saturated C.sub.5-21 alkyl group, a C.sub.5-21 alkenyl group or a C.sub.9-2, alcapolyenyl group with physiologically acceptable topical excipients for depigmenting and/or bleaching human skin and/or for removing pigmentation marks from the skin and/or for depigmenting hair and/or head hair.
Tyrosinase (monophenol dihydroxyl phenylalanine: oxygen oxidoreductase EC 1.14.18.1)) is the essential enzyme involved in this reaction sequence. It especially catalyses the reaction for the conversion of tyrosine into dopa (dihydroxyphenylalanine) and the reaction for the conversion of dopa into dopaquinone. This tyrosinase acts only when it is in the mature state, under the action of certain biological factors.
A substance is recognized as being depigmenting if it acts directly on the viability of the epidermal melanocytes in which melanogenesis takes place and/or if it interferes with one of the steps in the biosynthesis of melanin either by inhibiting one of the enzymes involved in melanogenesis or by becoming intercalated as a structural analogue of one of the chemical compounds in the melanin synthesis chain, whereby this chain may be blocked and ensure the depigmentation.
The substances most commonly used as depigmenting agents are, more particularly, hydroquinone and its derivatives, in particular its ethers such as hydroquinone monomethyl ether and monoethyl ether. Although they have a certain level of efficacy, these compounds are unfortunately not free of side effects on account of their toxicity, which can make them difficult or even hazardous to use. This toxicity arises from the fact that they interfere with fundamental mechanisms of melanogenesis, by killing cells which then risk disrupting their biological environment and which consequently force the skin to eliminate them by producing toxins.
Thus, hydroquinone is a compound which is particularly irritant and cytotoxic to melanocytes, and whose total or partial replacement has been envisaged by many investigators.
In order to overcome the drawbacks mentioned above, it has been envisaged, for example, to use derivatives of active compounds. Thus, U.S. Pat. No. 4,526,779 describes the use of fatty acid esters of hydroquinone as depigmenting agents. Unfortunately, these derivatives are less active than hydroquinone.
Substances have been sought which are not involved in the mechanism of melanogenesis, but which act upstream on tyrosinase by preventing its activation, and are consequently much less toxic. Kojic acid is commonly used as tyrosinase-activation inhibitor, this acid complexing the copper present in the active site of the enzyme. Unfortunately, this compound can give rise to allergic reactions ("Contact allergy to kojic acid in skin care products", M. Nakagawa et al, in Contact Dermatitis, January 95, Vol. 42 (1), pp. 9-13). In addition, this compound is unstable in solution, which somewhat complicates the manufacture of a composition containing it.
It is most particularly desired to use harmless topical depigmenting substances which are of good efficacy, in order to treat regional hyperpigmentations caused by melanocyte hyperactivity, such as idiopathic melasmas, occurring during pregnancy ("pregnancy mask" or chloasma) or during oestro-progestative contraception, localized hyperpigmentations caused by hyperactivity and proliferation of benign melanocytes, such as senile pigmentation marks known as actinic lentigo, accidental hyperpigmentations or depigmentations, possibly due to photosensitization or to post-lesional cicatrization, as well as certain leukodermias, such as vitiligo. For the latter, in which the cicatrizations can result in a scar which gives the skin a whiter appearance and leukodermias, failing being able to repigment the damage to the skin, the regions of residual normal skin are depigmented in order to give the skin as a whole a uniform white complexion.
Thus, there is a need for an agent for bleaching human skin, hairs and/or head hair which acts as effectively as known agents, but which does not exhibit their drawbacks, i.e. which is non-irritant, non-toxic and/or non-allergenic to the skin and which is stable in a composition.